The immunohistochemistry (IHC) laboratory is the primary CAP/CLIA certified laboratory performing tissue based immunohistochemical testing that subserves all LP diagnostic services. Immunohistochemical analysis of cancer and other diseases is essential for modern surgical pathology diagnostics, and plays an increasingly critical role in identifying targets for molecular and immunologically targeted therapies. For example the identification of cancer-associated antigens MART-1, GP-100, CEA, CD19, CD20, CD52, CD2, CD25, CD20, P53, NY-ESO-1, HER-2, EGFR, are necessary for enrollment into immune cell-based therapies developed by CCR Surgery Branch and/or antibody-based therapies developed by several other CCR Branches. Expression of a variety of tyrosine kinase receptors, including ERBB2 (HER2), EGFR, and C-KIT predict or influence response to therapies targeting their signaling pathways. In addition to performing this essential clinical service, the laboratory also provides research support to both Laboratory of Pathology clinical researchers and to the larger NCI/NIH community developing antibody based assays for interrogating novel targets using immunohistochemical methods. The immunohistochemistry core laboratory processed over 4200 cases in 2014, producing over 28,000 immunostained slides for clinical service. The laboratory produced an additional 1000 slides in support of a variety of research projects, requested by both LP clinical researchers and NCI/NIH researchers from outside of the Laboratory of Pathology. The laboratory tests include a panel of over 180 paraffin reactive antibodies, and 40 additional antibodies for frozen section studies. These include cell of origin diagnostic markers, cell signaling pathway activation markers, cell-type specific transcription factors, proliferation-related markers, and other prognostic markers. At any given time, the laboratory is developing or testing 5 or more novel antibodies for potential clinical or research use. Examples of new antibody tests developed by the service include type specific keratin antibodies, newly developed paraffin reactive CD markers including CD25, CD38, CD138, PD-1, PD-L1, CXCL13, tissue specific transcription factors and cell cycle regulators. Examples of the latter include MYF-4, CYCLIN D1, p27, HIF-1alpha, MITF, TFE3, FOXP3, OCT-2, OCT-4, BOB-1, PU-1, and several growth factor receptors such as c-KIT, EGRF, EGFRvIII and ERBB2. The laboratory is also developing assays to interrogate activated signaling pathway such as the PI3K/AKT, mTOR, and JAK/STAT pathways. Specific targets being developed include PTEN, and phosphorylated forms of AKT, S6K, MTOR, 4EBP1, STAT3, and STAT5b. Additional targets include mutated forms of EGFR (L858R, and EGFR exon 19 deletion variants), BRAF (V600E), and IDH1 (R132H) and a more a sensitive ALK antibody that can detect EL4-ALK fusion protein found in lung cancer. The immunohistochemistry core laboratory supports translational research of both NCI and NIH researchers, and in 2013 provided research support to multiple NCI and NIH laboratories, including the following NIH PIs: Dr. Elaine Jaffe (NCI), Dr. Wyndham Wilson (NCI), Dr. James Kochenderfer (NCI), Dr. Theo Heller (NIDDK), Dr. Steven Holland (NIAID), Dr. David Kleiner (NCI), Dr. Kenneth Kraemer (NCI), Dr, Stefania Pittaluga (LP-NCI), Dr. Steven Rosenberg (NCI), Dr. Martha Quezado (NCI), Dr. Tim Greten, Dr. Katherine Warren (NCI), Dr. Adrian Weistner (NHLBI), Dr. Raphaela Goldbach-Mansky.